title: Biological activity of three novel complexes with the ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one against Leishmania spp.
abstract: OBJECTIVE
  We report on new 1,2,4-triazolo[1,5-a]pyrimidine complexes that have been developed and examined for both antiproliferative in vitro activity against Leishmania infantum and Leishmania braziliensis, and report their possible mechanism of action on L. infantum and L. braziliensis.
  
  
  RESULTS
  Antileishmanial effects are described for newly synthesized Cu(II) and Co(II) complexes containing 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) as a ligand. These complexes display a wide structural diversity: (i) mononuclear unit, [Cu(HmtpO)2(H2O)3](ClO4)2·H2O (1); (ii) two-dimensional framework, {[Cu(HmtpO)2(H2O)2](ClO4)(2)·2HmtpO}n (2); and (iii) chains, {[Co(HmtpO)(H2O)3](ClO4)(2)·2H2O}n (3). Compounds 1 and 2 appeared to be the most active against L. infantum (IC50 20.0 and 24.4 μM, respectively), and compounds 1 and 3 the most active against L. braziliensis (IC50 22.1 and 23.5 μM, respectively), with IC50s similar to those of the reference drug, glucantime (18.0 μM for L. infantum and 25.6 μM for L. braziliensis). These compounds were not toxic towards J774.2 macrophages. IC25 decreased infection capacity and severely reduced the multiplication of intracellular amastigotes, following the trend 1>3>2 for L. infantum and 3>1>2 for L. braziliensis. These complexes had an effect on the energy metabolism of the parasites at the level of the NAD+/NADH balance and the organelle membranes, causing their degradation and cell death.
  
  
  CONCLUSIONS
  Cellular proliferation, metabolic and ultrastructural studies showed that the compounds 2>1>3 were highly active against L. infantum and L. braziliensis.
authors.affiliation: Department of Parasitology, University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ramírez-Macías
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Salas
authors.forename: Ana
authors.initials: A
authors.lastname: Caballero
authors.forename: María José
authors.initials: MJ
authors.lastname: Rosales
authors.forename: Noelia
authors.initials: N
authors.lastname: Villegas
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-Dieguez
authors.forename: Elisa
authors.initials: E
authors.lastname: Barea
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018314:Leishmania infantum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015388:Organelles / Q000648:ultrastructure; D021261:Parasitic Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D011743:Pyrimidines; D014230:Triazoles